Cargando…

NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment

We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant ce...

Descripción completa

Detalles Bibliográficos
Autores principales: North, William G, Gao, Guohong, Jensen, Amy, Memoli, Vincent A, Du, Jinlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262385/
https://www.ncbi.nlm.nih.gov/pubmed/22291485
_version_ 1782221718945792000
author North, William G
Gao, Guohong
Jensen, Amy
Memoli, Vincent A
Du, Jinlin
author_facet North, William G
Gao, Guohong
Jensen, Amy
Memoli, Vincent A
Du, Jinlin
author_sort North, William G
collection PubMed
description We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant cell line NCI H82, and by most SCLC tumors, and that these receptors are important for the growth of human SCLC tumor xenografts in mice. Reverse transcription-polymerase chain reaction demonstrated mRNA for both receptors, with sequences identical to those for human mRNAs, are expressed in all four cell lines, and these generated proteins of the expected sizes 120 and 170 kDa. Cell viability tests showed cell growth was significantly (P < 0.0001) impaired by NMDAR1 antagonists MK-801 and memantine. Ifenprodil and Ro25-6981, NMDAR2B antagonists at the polyamine site, also significantly (P < 0.001) inhibited the growth/survival of these cells. Alternatively, the glycine-binding antagonist, L701, 324, increased viability to 140% and 120% in NCI H345 and NCI H82 cells after 48 hours of incubation. Immunohistochemistry of SCLC tumors with our polyclonal antibodies gave specific positive staining for the NMDAR1 receptor in 8 of 10 tissues examined. Small amounts of these same antibodies significantly reduced the growth of NCI-H345 cells up to 25% (P < 0.001). When NCI H345 cells were grown as tumor xenografts in mice, the growth of these tumors was reduced by 60% (P < 0.001) by treatments with MK-801 over five days. All of these data point to active NMDAR receptors possibly having an important influence on SCLC growth and survival.
format Online
Article
Text
id pubmed-3262385
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-32623852012-01-30 NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment North, William G Gao, Guohong Jensen, Amy Memoli, Vincent A Du, Jinlin Clin Pharmacol Original Research We previously showed that functional N-methyl-D-aspartate (NMDA) receptors are expressed by human neuroblastoma cells. In this study we demonstrate functional NMDAR1 and NMDAR2 receptors are expressed by small-cell lung cancer (SCLC) classical cell lines NCI H146, NCI H345, and DMS 53, by variant cell line NCI H82, and by most SCLC tumors, and that these receptors are important for the growth of human SCLC tumor xenografts in mice. Reverse transcription-polymerase chain reaction demonstrated mRNA for both receptors, with sequences identical to those for human mRNAs, are expressed in all four cell lines, and these generated proteins of the expected sizes 120 and 170 kDa. Cell viability tests showed cell growth was significantly (P < 0.0001) impaired by NMDAR1 antagonists MK-801 and memantine. Ifenprodil and Ro25-6981, NMDAR2B antagonists at the polyamine site, also significantly (P < 0.001) inhibited the growth/survival of these cells. Alternatively, the glycine-binding antagonist, L701, 324, increased viability to 140% and 120% in NCI H345 and NCI H82 cells after 48 hours of incubation. Immunohistochemistry of SCLC tumors with our polyclonal antibodies gave specific positive staining for the NMDAR1 receptor in 8 of 10 tissues examined. Small amounts of these same antibodies significantly reduced the growth of NCI-H345 cells up to 25% (P < 0.001). When NCI H345 cells were grown as tumor xenografts in mice, the growth of these tumors was reduced by 60% (P < 0.001) by treatments with MK-801 over five days. All of these data point to active NMDAR receptors possibly having an important influence on SCLC growth and survival. Dove Medical Press 2010-04-01 /pmc/articles/PMC3262385/ /pubmed/22291485 Text en © 2010 North et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
North, William G
Gao, Guohong
Jensen, Amy
Memoli, Vincent A
Du, Jinlin
NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
title NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
title_full NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
title_fullStr NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
title_full_unstemmed NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
title_short NMDA receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
title_sort nmda receptors are expressed by small-cell lung cancer and are potential targets for effective treatment
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262385/
https://www.ncbi.nlm.nih.gov/pubmed/22291485
work_keys_str_mv AT northwilliamg nmdareceptorsareexpressedbysmallcelllungcancerandarepotentialtargetsforeffectivetreatment
AT gaoguohong nmdareceptorsareexpressedbysmallcelllungcancerandarepotentialtargetsforeffectivetreatment
AT jensenamy nmdareceptorsareexpressedbysmallcelllungcancerandarepotentialtargetsforeffectivetreatment
AT memolivincenta nmdareceptorsareexpressedbysmallcelllungcancerandarepotentialtargetsforeffectivetreatment
AT dujinlin nmdareceptorsareexpressedbysmallcelllungcancerandarepotentialtargetsforeffectivetreatment